Intellectual disability (ID) is still unexplained in 60% of cases and prenatal diagnosis
is very challenging for this condition. A second gravida presented to us at 6 weeks
of gestation for counseling. Her previous child had been diagnosed with ID and autism.
Detailed family history showed that her brother also had ID. Screening investigations
were normal for the affected child. Exome sequencing report revealed variation of
unknown significance (VOUS) on SIN3A gene and UPF3B gene. The variation in X-linked UPF3B gene was reclassified as novel pathogenic variation after segregation studies with
parents and affected maternal uncle for both the genes variations. An amniocentesis
was done at 18 weeks gestation for the novel mutation in the UPF3B gene and the fetus was found unaffected. The patient delivered a healthy male child
who is doing well at two years of age. To conclude, we should not disregard VOUS on
exome sequencing. Identification of VOUS requires careful genotype-phenotype correlation
and segregation studies to counsel parents regarding the risk of having another affected
child.
Keywords
Intellectual disability - X-linked - Autism -
UPF3B gene - Variation
